The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
The no observable adverse effect level for male mice was 2.5 mg of pentamidine isethionate/kg/day. Dosages of 5 and 10 mg of pentamidine isethionate/kg/day caused some reduced body weight gains in male mice. Transient hypoactivity was detected in male and female (b) mice in the 10 mg/kg/day dose group. The NOAEL for general toxicity for female mice was 5 mg/kg/day. Dosages of 10 mg of pentamidine isethionate/kg/day and higher caused mortality, decreased body weights, and clinical observations of toxicity ranging from hypoactivity to seizures. The NOAEL for developmental toxicity was 10 mg of pentamidine isethionate/kg/day. Dosages of 20 mg of pentamidine isethionate/kg/day produced decreased fetal body weights.The toxicity of pentamidine isethionate was assessed in Swiss male and female mice by intravenous administration at dose levels ranging from 2 .5 to 40 mg/kg/day. Male mice (10/group) were dosed with 2.5, 5, and 10 mg of the test article/kg/day on study days 5 to 24 and were sacrificed on day 25. Prior to dosing (study days 0 to 4) the male mice were cohabited with female mice (20/group), designated as females. The sperm-positive female mice were dosed at 2.5, 5, and 10 mg of pentamidine isethionate/kg/day on days 6 through 15 of gestation and were sacrificed on scheduled day 4 of lactation. A second group of female mice (20/group), designated as females (a), was dosed with 5, 10, 20, and 40 mg of pentamidine isethionate/kg/day beginning on study day 0 and throughout mating on study days 9 to 13 until the day prior to scheduled sacrifice on scheduled Day 18 of gestation. All female mice treated with 40 mg of pentamidine isethionate/kg/day died prior to mating. Adult mice were evaluated for clinical signs, body weights, and clinical pathology parameters. Male mice were subjected to a sperm function evaluation. Offspring from each group were evaluated for viability, external anomalies, and weight.